Division of Endocrinology Diabetes and Metabolism, Virginia Commonwealth University, Richmond, VA, United States.
Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, United States.
Front Endocrinol (Lausanne). 2022 Feb 28;13:843539. doi: 10.3389/fendo.2022.843539. eCollection 2022.
The pharmacokinetics of liothyronine causes concerns for cardiovascular toxicity. While the effects of sustained increase in serum T3 concentrations are well described, little is known on the effects of acute changes in T3 concentrations due to rapid action of thyroid hormone.
To assess the clinical relevance of transient increase of T3 levels on cardiovascular system and energy metabolism.
Double-blind, three arms, placebo controlled, cross-over study (ClinicalTrials.gov Identifier: NCT03098433).
Twelve volunteers (3 females, 9 males), age 27.7 ± 5.1 years.
Oral administration of liothyronine 0.7 mcg/kg, equimolar dose of levothyroxine (0.86 mcg/kg), or placebo in three identical study visits. Blood samples for total T3, free T4 were collected at times 0', 60' 120' 180' 240'. Continuous recording of heart rate, blood pressure, and hemodynamic data was performed using the volume clamp method. Resting energy expenditure was measured by indirect calorimetry. An echocardiogram was performed on each study visit at baseline and after the last blood sampling.
Changes in cardiovascular function and energy expenditure.
Following the administration of liothyronine, serum T3 reached a C of 421 ± 57 ng/dL with an estimated T of 120 ± 26 minutes. No differences between study arms were observed in heart rate, blood pressure, hemodynamics parameters, energy expenditure, and in echocardiogram parameters.
The absence of measurable rapid effects on the cardiovascular system following a high dose of liothyronine supports the rationale to perform long-term studies to assess its safety and effectiveness in patients affected by hypothyroidism.
左甲状腺素的药代动力学引起了人们对心血管毒性的关注。虽然血清 T3 浓度持续升高的影响已有详细描述，但由于甲状腺激素的快速作用，对 T3 浓度急性变化的影响知之甚少。
评估 T3 水平短暂升高对心血管系统和能量代谢的临床相关性。
双盲、三臂、安慰剂对照、交叉研究（ClinicalTrials.gov 标识符：NCT03098433）。
12 名志愿者（3 名女性，9 名男性），年龄 27.7 ± 5.1 岁。
在三次相同的研究访问中，志愿者分别口服左甲状腺素 0.7 mcg/kg、等量的左甲状腺素钠（0.86 mcg/kg）或安慰剂。在 0'、60'、120'、180'和 240'时采集总 T3、游离 T4 的血样。使用容积钳夹法连续记录心率、血压和血液动力学数据。通过间接测热法测量静息能量消耗。在每次研究访问时，在基线和最后一次采血后进行超声心动图检查。
心血管功能和能量消耗的变化。
给予左甲状腺素后，血清 T3 达到 421 ± 57ng/dL，T1/2 为 120 ± 26 分钟。在心率、血压、血液动力学参数、能量消耗和超声心动图参数方面，各研究组之间没有差异。
在高剂量左甲状腺素给药后，心血管系统没有可测量的快速作用，这支持了进行长期研究以评估其在甲状腺功能减退症患者中的安全性和有效性的合理性。
